Table 2.
Potential radionuclide conjugates for breast cancer
| Isotope | Status | Antibody | Model | Potency/Efficacy |
|---|---|---|---|---|
| 177Lu (chelated) | Pilot clinical study | Trastuzumab | HER2‐positive breast cancer patients | No drug uptake for HER2‐negative patients, whereas the radioimmunoconjugate retains its integrity up to 7 days in vivo.8 |
| 213Bi (chelated) | In vivo | Antibody to human aspartyl β‐hydroxylase | 4T1 tumor mice | Significant effect on the tumor.92 |
| 213Bi (chelated) | In vivo | Antibody to chondroitin sulfate proteoglycan 4 | TNBC xenograft and in vitro | Significantly inhibited tumor and cell growth.53 |
| 225Ac (chelated) | Anti‐rat HER2′/In vivo | Anti‐rat HER2 | Metastatic breast cancer mouse model | Complete eradication of lung metastasis and more efficacious than213Bi.103 |
| 111In/90Y (peptide linked) | Phase I | M170 | Advanced breast cancer patients | Patients had grade 3 or 4 myelosuppression93 |
| 213Bi (chelated) | In vivo | Plasminogen activator inhibitor‐2 | MDA‐MB‐231 cell inoculation in mice | Inhibit growth at 2 days after inoculation.2 |
| 90Y (chelated) | In vivo | Cilengitide | HBT 3477 cell xenografted mice | Increased efficacy compared to radiotherapy/cilengitide alone9 |
| 131I | In vivo | Humanized anti‐Lewis Y | MCF‐7 xenografted mouse | Significant tumor growth inhibition compared to control radiolabeled antibody15 |
| 131I | In vivo | 131I‐IgG2a (rat) | MDA‐MB‐361 xenograft | Tumor growth inhibition for more than 24 days 101 |
| 111In/90Y | Phase I | IgG1 (BrE3) | Metastatic breast cancer patients | Risk of developing HAMA response 19 |
| 131I | Pilot clinical study | 131I‐IgG1 (ChL6) | Metastatic breast cancer patients | Partial response achieved with the development of thrombocytopenia and granulocytopenia20, 21 |
Radiation emitted from a radionuclide can be used to kill cells. Radioactive compounds can also attack noncancerous cells; therefore, targeted delivery of the radionuclide with the help of a monoclonal antibody is desirable. The radionuclide can be linked to a monoclonal antibody by a linker, or the antibody could be labeled with radioisotope by a chelation method (Figure 2B).